Polymers and copolymers are widely used in a variety of fields. One reason for the expansive application of polymers is due to the uniquely differing physical properties which are exhibited by various polymers. Numerous different polymers, all exhibiting varying physical properties, can be obtained from the same monomers by altering the method of preparation, the polymerization catalysts, the quantities of monomers utilized and related factors.
The prior art teaches a number of polymers and copolymers of lactic acid and glycolic acid. Schmitt et al., in U.S. Pat. Nos. 3,739,773, 3,736,646 and 3,875,937, cite and discuss a great deal of art directed to polymers and copolymers in general, as well as specific lactic acid and glycolic acid copolymers.
As pointed out by Yolles in U.S. Pat. No. 3,887,699, much interest has been focused on the possibility of incorporating drugs into polymeric materials in order to obtain a controlled and sustained release of such drug to a living system. Many problems, however, are associated with the use of polymers and copolymers for the slow release of drugs into a living system. For example, Schmitt et al., in U.S. Pat. No. 3,982,543, points out that copolymers in general have a relatively slow hydrolysis rate in the acid environment in the stomach but a much higher hydrolysis rate in the more alkaline environment of the intestine. Siegrist et al., in U.S. Pat. No. 3,535,419, disclose a sustained release drug and polymer formulation that is suitable for the administration of steroidal drugs via the rumeno-reticular portions of the stomach of ruminants. Such formulations require the use of at least one highly water insoluble wax, fat, oil, fatty acid, fatty acid ester, fatty acid amide, fatty acid alcohol or polymer. Reuter et al., in U.S. Pat. No. 4,011,312, describe a prolonged release drug dosage form for the treatment of bovine mastitis consisting of an antimicrobial agent dispersed in a matrix of a polyester of glycolic and lactic acids having a molecular weight of less than 2000.
Numerous references teach that an advantage of utilizing copolymers comprised of glycolic acid and lactic acid is the fact that the hydrolysis products are constituents in normal metobolic pathways and consequently are nontoxic and harmless when exposed to human or animal tissues. One drawback associated with the prior art copolymers, however, is the presence of polymerization catalysts such as a polyvalent metal oxide or metal halide. Upon biodegradation of the copolymer-drug matrix, a finite quantity of such toxic polymerization catalyst remains in the animal tissue and is not subject to biodegradation. Moreover, catalysts utilized to promote polymerization also cause breakdown of the polymer when contact is maintained. Therefore, polymers containing polymerization catalysts as impurities are subject to unpredictable degradation.
An object of this invention is to provide a process for polymerizing glycolic acid and lactic acid via condensation, such that copolymers having a molecular weight of about 6000 to about 35000 are obtained. A further object is to provide a polymerization process which permits the substantially total removal from the copolymer of polymerization catalysts, so that the copolymers so produced can be utilized as drug delivery systems, thereby permitting the complete biodegradation of the system with no residual toxic foreign substances remaining in animal tissues. A further object of the invention is to provide unique copolymers derived from lactic and glycolic acid which are capable of biodegradation over a predetermined period of time, thus allowing the controlled release of a drug dispersed therein at a predetermined rate over the period of time necessitated by the particular treatment being afforded. Still another object of the invention is to provide a method for polymerizing lactic acid and glycolic acid via direct condensation, thereby obviating the need to first prepare cyclic lactides and glycolides as preferred by the prior art. The invention therefore offers significant economic advantages over prior art polymerization processes.